(Montgomery, Sherman, Nagorny) Carbohydrates are essential structural motifs that play a key role in many biological processes. They provide the primary structural features that govern many molecular recognition events that are central in biology. Essential molecular properties such as protein folding, biological target recognition, stability, and distribution are governed by glycosidic positioning and structure. Furthermore, alteration of glycosidic functionality has been demonstrated to enhance the potency and specificity of pharmaceutically important compounds. Despite the key role that carbohydrates play in biology and their promise in strategies for the improvement of human health, significant hurdles exist in the efficient access to rare and high-value monosaccharides and their chemical manipulation. Many sugars that are essential in governing the bioactivity of natural products and that hold promise for the discovery of new structures that could impact human health are currently not available to the scientific community. Furthermore, those that are available typically require complex synthetic manipulations that are beyond the expertise of scientists who are not specialists in organic synthesis. The major objective of this research proposal is to develop synergies between methods in biosynthesis and small molecule catalysis to overcome these barriers that are limiting progress in glycoscience. Through innovative biosynthetic strategies, efficient access to rare, high-value monosaccharides will be obtained. The approach brings together state-of-the-art advances in genome mining, synthetic biology, and biotransformation technologies. These advances will partner with novel approaches using transition metal catalysts and organocatalysts to convert biosynthetically derived monosaccharides into versatile and widely available reagents for the stereoselective construction of glycosidic bonds. Additionally, methods will be devised to convert common, widely available monosaccharides into rare sugars through redox manipulations. Innovative techniques in synthesis involving newly devised chiral phosphoric acid catalysts and carbohydrate-derived silane reagents will be developed in the course of the proposed studies. An innovative approach for solid- phase monosaccharide capture and synthetic elaboration will be developed. The unique multidisciplinary perspective of this effort will allow the development of strategies that cannot be addressed by conventional approaches. The outcome will be greatly improved access to valuable reagents and innovative methods for the assembly of glycosylated structural motifs that will enable progress in glycoscience that is currently hindered by limitations and difficulties of current approaches.